Abstract
Repetitive ectopic discharges from injured afferent nerves play an important role in initiation and maintenance of neuropathic pain. Gabapentin is effective for treatment of neuropathic pain but the sites and mechanisms of its antinociceptive actions remain uncertain. In the present study, we tested a hypothesis that therapeutic doses of gabapentin suppress ectopic afferent discharge activity generated from injured peripheral nerves. Mechanical allodynia, induced by partial ligation of the sciatic nerve in rats, was determined by application of von Frey filaments to the hindpaw. Single-unit afferent nerve activity was recorded proximal to the ligated sciatic nerve site. Intavenous gabapentin, in a range of 30 to 90 mg/kg, significantly attenuated allodynia in nerve-injured rats. Furthermore, gabapentin, in the same therapeutic dose range, dose-dependently inhibited the ectopic discharge activity of 15 injured sciatic afferent nerve fibers through an action on impulse generation. However, the conduction velocity and responses of 12 normal afferent fibers to mechanical stimulation were not affected by gabapentin. Therefore, this study provides electrophysiological evidence that gabapentin is capable of suppressing the ectopic discharge activity from injured peripheral nerves. This action may contribute, at least in part, to the antiallodynic effect of gabapentin on neuropathic pain.
Footnotes
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Send reprint requests to: Hui-Lin Pan, M.D., Ph.D., Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1009. E-mail: hpan{at}wfubmc.edu
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↵1 This study was supported by grant GS-30 (to H.-L.P.) from the American Heart Association, Mid-Atlantic Affiliate and by Grants HL-60026 (to H.-L.P.) and GM-35523 (to J.C.E.) from the National Institutes of Health.
- Abbreviation:
- GABA
- γ-aminobutyric acid
- Received July 17, 1998.
- Accepted October 8, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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